# A novel combinatorial approach to restore motor function after spinal cord injury

> **NIH NIH R01** · WINIFRED MASTERSON BURKE MED RES INST · 2020 · $398,655

## Abstract

Abstract (Summary): Spinal cord injury (SCI) often causes permanent paralysis due to
failure of injured axons to regenerate. Although injured CS axons do not re-grow beyond
the lesion after SCI, they form new connections with propriospinal neurons above
(rostral to) the lesion which contributes to the limited recovery seen in these injury
models. In this study, we propose two-pronged strategies to simultaneously induce re-
growth of injured corticospinal (CS) axons beyond the lesion site and enhance
remodeling of connectivity between injured CS axons and propriospinal neurons after
SCI. CS axonal growth can be promoted by reducing phosphatase and tensin homolog
(Pten) activity in the sensorimotor cortex. Our preliminary data reveal increased CS
connectivity after SC in mice lacking PlexA1 encoding a semaphorin6D receptor. Since
injured CS axons in PlexA1 mutants do not pass beyond the lesion site, our preliminary
data strongly suggest that new connections between injured CS axons and propriospinal
neurons are enhanced through the uninjured ventral regions after SCI to compensate for
the loss of CS inputs. Based on these preliminary data, the central hypothesis of this
proposal is that a combined modulation of Sema6D-PlexA1 and Pten signaling will
facilitate rewiring of CS connectivity with propriospinal neurons as well as re-growth of
injured CS axons after SCI at cervical levels. Therefore, these interventions will improve
functional CS connectivity and motor recovery. In Aim 1, we will determine whether
deletion of both PlexA1 and Pten in the sensorimotor cortex will enhance connectivity
between injured CS axons and propriospinal neurons to a greater degree than the loss
of PlexA1 or Pten alone. In Aim 2, we will determine whether PlexA1, Pten, or
PlexA1/Pten deletion increases circuits between injured CS neurons and muscles.
Finally, in Aim 3, we will examine whether motor recovery is enhanced in mice lacking
PlexA1 and Pten in the sensorimotor cortex.

## Key facts

- **NIH application ID:** 9894862
- **Project number:** 5R01NS100772-05
- **Recipient organization:** WINIFRED MASTERSON BURKE MED RES INST
- **Principal Investigator:** Yutaka Yoshida
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $398,655
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894862

## Citation

> US National Institutes of Health, RePORTER application 9894862, A novel combinatorial approach to restore motor function after spinal cord injury (5R01NS100772-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9894862. Licensed CC0.

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